Clinical outcomes of carvedilol versus metoprolol in patients with heart failure with preserved ejection fraction following myocardial infarction

Purpose Optimal beta-blocker selection in patients with heart failure with preserved ejection fraction (HFpEF) following acute myocardial infarction (MI) remains uncertain. While both carvedilol and metoprolol are commonly prescribed, comparative effectiveness data in HFpEF are limited. We evaluated 3-year cardiovascular outcomes associated with carvedilol versus metoprolol initiation within 1 month after MI in patients with HFpEF. Methods We conducted a retrospective cohort study using the TriNetX Research Network (106 healthcare organizations). Adults ≥18 years with HFpEF (left ventricular ejection fraction ≥50% and ICD-10 I50), without atrial fibrillation, and with acute MI (ICD-10 I21) were included. Patients initiated on metoprolol (RxNorm 6918) or carvedilol (RxNorm 20352) within 1 month of MI were identified. The index date was defined as the first qualifying beta-blocker prescription after MI. Outcomes were assessed from 14 to 1,095 days post-index. Primary outcomes included all-cause mortality and acute heart failure (AHF). Secondary outcomes included recurrent MI (STEMI), hospitalization, stroke, ventricular tachycardia (VT), and cardiac arrest. Propensity score matching balanced demographics, cardiovascular comorbidities, and laboratory parameters, yielding 1,537 patients per group. Results After matching, the mean age was 70.7±13.3 years, with balanced comorbidities. Over 3 years, mortality did not differ significantly between metoprolol and carvedilol (15.1% vs 15.7%; hazard ratio [HR] 0.94, 95% CI 0.78–1.13; log-rank p=0.511). Recurrent MI risk was similar (4.8% vs 5.1%; HR 0.92, 95% CI 0.67–1.27; p=0.618). Hospitalization rates were comparable (27.1% vs 28.2%; HR 0.94, 95% CI 0.82–1.07; p=0.337). Notably, acute heart failure occurred less frequently in the metoprolol group (15.5% vs 18.2%; risk difference −2.7%; HR 0.81, 95% CI 0.68–0.97; log-rank p=0.019). Stroke (6.1% vs 6.1%; HR 1.00, p=0.979), VT (2.9% vs 2.9%; HR 1.01, p=0.969), and cardiac arrest (3.2% vs 3.3%; HR 0.95, p=0.789) were similar between groups. Conclusions In patients with HFpEF following MI, metoprolol and carvedilol were associated with comparable 3-year mortality, recurrent MI, hospitalization, and arrhythmic outcomes. However, metoprolol use was associated with a modest but statistically significant reduction in acute heart failure events. These findings suggest that in HFpEF patients post-MI, beta-blocker selection may not meaningfully impact survival or ischemic risk, but metoprolol may confer a lower risk of heart failure exacerbations. Prospective trials are warranted to clarify whether beta-1 selective versus nonselective beta-blockade differentially influences long-term outcomes in this population.